T cell and B cell antigen receptors share a conserved core transmembrane structure

Area of Science:

• Immunology
• Structural Biology
• Molecular Cell Biology

Background:

• B cell receptors (BCRs) and T cell receptors (TCRs) are crucial for adaptive immunity, mediating antigen recognition and signal transduction.
• Both receptors consist of variable antigen-binding modules and invariant signaling modules, but their structural similarities at the membrane interface were not fully understood.

Purpose of the Study:

• To investigate whether the B cell receptor (BCR) possesses a transmembrane (TM) structure analogous to the well-characterized TCR TM interface.
• To determine the role of this potential BCR TM structure in receptor assembly and stability.

Main Methods:

• Biochemical analysis of mouse IgM BCR.
• Computational modeling and molecular dynamics simulations.
• Comparison with cryo-electron microscopy (cryo-EM) structures of human BCRs.

Main Results:

• A core TM structure, similar to that of the TCR, was identified in the mouse IgM BCR.
• This BCR TM structure is stabilized by interhelical hydrogen bonds and is essential for assembly with the CD79AB signaling module.
• Molecular dynamics simulations suggest all five BCR isotypes can form comparable TM structures.

Conclusions:

• BCRs and TCRs utilize a common, evolutionarily conserved core TM structure for receptor assembly and membrane stability.
• This shared structural motif underscores a fundamental principle in immune receptor complex formation across different immune cell types.